Vildagliptin dihydrate (LAF237 dihydrate)

Vildagliptin (LAF237 dihydrate;NVP-LAF 237 dihydrate) is a dipeptidyl peptidase 4 (DPP4) inhibitor that delays the degradation of glucagon-like peptide-1 (GLP-1).

Treatment of obese diabetic mice with 1 mg/kg/day Vildagliptin or with 10 mg/kg/day valsartan for 8 weeks increases pancreatic islet β-cell density and stimulates islet β-cell proliferation while preventing apoptosis and islet fibrosis and decreasing superoxide production and nitrotyrosine formation. The combination of both compounds significantly magnifies the beneficial effect of either monotherapy[1]. Valsartan or Vildagliptin pretreatment significantly increases plasma GLP-1 expression, reduces apoptosis of endothelial cells isolated from diabetic mice aorta. The expression of NADPH oxidase subunits also significantly decreases resulting in decreased superoxide production and ICAM-1 (fold change: valsartan : 7.5±0.7, P<0.05; LAF237: 10.2±1.7, P<0.05), VCAM-1 (fold change: valsartan : 5.2±1.2, P<0.05; LAF237: 4.8±0.6, P<0.05), and MCP-1 (fold change: valsartan: 3.2±0.6, LAF237: 4.7±0.8; P<0.05) expression. Moreover, the combination treatment with valsartan and Vildagliptin results in a more significant increase of GLP-1 expression. The decrease of the vascular oxidative stress and inflammation reaction is also higher than monotherapy with valsartan or Vildagliptin[2]. Daily oral administration of Vildagliptin (5 mg/kg) alone or in combination with Pioglitazone (20 mg/kg) for 7 weeks significantly reduces blood glucose levels and HbA1c. It increases serum insulin levels and decreases serum glucagon. It also shows a strong anti-oxidant activity[3].

[1]. Cheng Q, et al. Combination of the dipeptidyl peptidase IV inhibitor LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] with the angiotensin II type 1 receptor antagonist valsartan [N-(1-oxopentyl)-N-[[2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl]methyl]-L-valine] enhances pancreatic islet morphology and function in a mouse model of type 2 diabetes. J Pharmacol Exp Ther. 2008 Dec;327(3):683-91. [2]. Shen M, et al. The synergistic effect of valsartan and LAF237 [(S)-1-[(3-hydroxy-1-adamantyl)ammo]acetyl-2-cyanopyrrolidine] on vascular oxidative stress and inflammation in type 2 diabetic mice. Exp Diabetes Res. 2012;2012:146194. [3]. Abdelhamid AM, et al. Vildagliptin/Pioglitazone Combination Improved The Overall Glycemic Control In Type I Diabetic Rats. Can J Physiol Pharmacol. 2018 Mar 6. doi: 10.1139/cjpp-2017-0680.